MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection.
MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection.
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DOI：
10.1038/s41598-021-02242-x
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发表时间：
2021-11-22
影响因子：
4.6
通讯作者：
Goldblum SE
中科院分区：
文献类型：
--
作者：
Verceles AC;Bhat P;Nagaria Z;Martin D;Patel H;Ntem-Mensah A;Hyun SW;Hahn A;Jeudy J;Cross AS;Lillehoj EP;Goldblum SE
We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.
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DOI：
10.1126/science.1223012
发表时间：
2012-08-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Button B;Cai LH;Ehre C;Kesimer M;Hill DB;Sheehan JK;Boucher RC;Rubinstein M
通讯作者：
Rubinstein M
DOI：
10.1099/00221287-13-3-572
发表时间：
1955-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
HOLLOWAY, BW
通讯作者：
HOLLOWAY, BW
影响因子：
11.8
作者：
Kalil, Andre C.;Metersky, Mark L.;Brozek, Jan L.
通讯作者：
Brozek, Jan L.
影响因子：
5.8
作者：
Chmiel JF;Davis PB
通讯作者：
Davis PB
影响因子：
3.1
作者：
Feldman, M;Bryan, R;Prince, A
通讯作者：
Prince, A